Several polypeptide factors present in the thymus gland have been implicated to play important roles in the development and maintenance of immunological competance in man and in animals. The importance of the immune system in the defense against cancer and tumor cells is now widely recognized. In recent years, a few polypeptides shown to be able to stimulate maturation, differention and function of T cells have been isolated from bovine thymus. Among them, the peptide thymosin .alpha..sub.1 has been intensively studied. Its structure and activity have been described in U.S. Pat. No. 4,079,127.
Additionally, in the course of synthesizing thymosin .alpha..sub.1 by solution phase methodology, Wang in U.S. Pat. No. 4,148,788 utilized the protected carboxyl terminal octa-, undeca- and tetradecapeptides of thymosin .alpha..sub.1 as intermediates. These compounds were also deprotected by hydrogenolysis followed by treatment with HF and the resulting free peptides were indicated to have activity in the regulation, differentiation and function of T-cells.
In addition, this patent described the preparation and use as intermediates in the synthesis of thymosin .alpha..sub.1 of the protected carboxyl terminal tripeptide Ala--Glu(OBzl)--Asn--OBzl and the protected carboxyl terminal pentapeptide H--Glu(OBzl)--Glu(OBzl)--Ala--Glu(OBzl)--Asn--OBzl. No teaching or suggestion appears in this patent to deprotect either of these compounds nor is there any suggestion that the resulting free peptides might exhibit immunostimulatory activity.
The carboxyl terminal tetrapeptide in protected form, i.e., H--Glu(OBu.sup.t)--Ala-Glu(OBu.sup.t)--Asn(MbH)OBzl where Bu.sup.t =tert. butyl and MbH=4,4'dimethoxybenzhydryl has been described by Birr and Stollenwerk, in Angew. Chem., 91, 422 (1979) as an intermediate in the synthesis of thymosin .alpha..sub.1 by an alternate scheme from that suggested by Wang, supra. However, there is no teaching or suggestion in this paper that such compound be deprotected to the free peptide or that such free peptide, if prepared, would exhibit immunostimulatory activity.